Geneticists use CRISPR to cut toxic protein out of the aging equation

Date: 22.2.2019

There is much we don't understand about the aging of the human body, but working with what we do know researchers continue to uncover potential new ways to slow down the process. Among them is a team of genetic scientists at the Salk Institute, which has developed a new therapy using the CRISPR/Cas9 tool that has greatly boosted the lifespan of rapidly aging mice.

The work carried out in the Salk Institute's Gene Expression Laboratory involved mice engineered with a very rare genetic condition known as Hutchinson-Gilford progeria syndrome, or simply progeria. Caused by a mutation in the LMNA gene, the condition affects one in four million babies worldwide and leads to rapid aging, with the average life expectancy for a child born with progeria around 13 years.

Progeria is not the only degenerative disease caused by a mutation in the LMNA gene, but it is one of the most severe. In a healthy subject, the gene codes for two proteins called lamin A and lamin C. In progeria patients, it instead produces a shorter, toxic version of lamin A called progerin, which builds up quickly with and accelerates the aging process.

Reddy and her colleagues sought to limit the buildup of progerin by targeting the LMNA gene in the mice to blanket its toxicity. To do this, they delivered the CRISPR/Cas9 gene editing tools using an adeno-associated virus (AAV), which carried them to the right place on the DNA in order to make a critical cut and prevent the lamin A and progerin proteins from functioning, without impacting lamin C.

The scientists watched on as the treated mice became stronger and more active after two months, exhibiting improved cardiovascular health. The treatment also appeared to delay common symptoms of progeria and old age: degenerating arterial blood vessels and bradycardia (an abnormally slow heart rate). Ultimately, the treatment restored the activity levels of the progeria-afflicted mouse models to those of normal, healthy mice and increased their life span by around 25 percent.